Our objectives are to understand the chemical mechanism(s) of action of insulin on glycogen synthesis, and the alterations in the absence of insulin in the diabetic state. We are interested in 3 principal molecular sites, the chemistry and enzymology of multiple phosphorylation sites of glycogen synthase; the direct insulin-mediated inhibition of the protein kinase and its molecular characteristics as well as the separate mechanism of glycogen synthase activation observed in the presence of glucose. Here the phosphoprotein phosphatase is activated. Next we are interested in isolating and understanding a novel low MW insulin mediated inhibitor of the protein kinase which may be a chemical messenger. Finally, we are interested in the active site of the insulin molecule responsible for its chemical mechanism of action upon interacting with the cell membrane receptor. Here we are working with degraded insulin and insulin fragments to identify the active site on the molecule.